Radiation enhancement of gemcitabine in two human squamous cell carcinoma cell lines

Background: Gemcitabine (dFdC) is a new nucleoside analogue with promising activity in different solid tumors. We investigated whether dFdC enhances t he effect of irradiation in human squamous carcinoma cells of the oropharyn x (#4197) and of the uterine cervix (HeLa) with special regard to the time- dose-relationship concerning dFdC and the dependence upon the timing of irr adiation. Materials and methods: Under standardized conditions monolayers o f cells were Exposed to various dFdC concentrations (0.003-10 mu mol/l) for different times_(4-24 h). Irradiation (0-6 Gy) followed immediately or 12 h after dFdC exposure (0.003-0.03 mu mol/l; 4-24 h). Results: The cytotoxic effect of dFdC depends on its concentration and the exposure duration. Exp osed to non and/or slightly cytotoxic concentrations (greater than or equal to 0.003-0.03 mu mol/l) for 4, 8 16 and 24 h and followed by immediate irr adiation the radiation enhancement ratio (RER) is 1.03-2.67 in #4197 cells and 1.04-2.47 in HeLa cells, respectively. Irradiated 12 h after 24 h expos ure (dFdC 0.01-0.03 mu mol/l) the RER is reduced to 1.10-1.17 (#4197) and 1 .18-1.72 (HeLa). Conclusions: Depending on the drug concentration, exposure duration, and timing of irradiation, dFdC enhances the irradiation effect on human squamous cell carcinoma cell lines (#4197 HeLa).